Wernicke's encephalopathy, and Korsakoff's psychosis are related disease entities shown to be associated with a depletion of cerebral thiamine. The precise cerebral biochemical mechanism responsible for these disorders is unknown. Previous studies have shown that defective decarboxylation of pyruvic acid may be an important feature in the development of neurological symptoms in thiamine deficient rats. This is based on the observation that as the symptoms of thiamine deficiency are "reversed" with thiamine administration, decreased pyruvate decarboxylase activity reverts toward normal. The activity of the other major thiamine dependent enzyme, transketolase, does not reverse with thiamine administration. The significance of the decrease in pyruvate decarboxylase is somewhat unclear since net ATP and acetylcholine levels remain unchanged in thiamine deficient rat brain. However, these studies have not assessed metabolic flux in thiamine deficiency. Similarily, there are no animal studies directly examining the effect on pyruvate decarboxylase and metabolic flux of the "sparing" effect of fat and alcohol, and the "inducing" effect of glucose observed in patients with the Wernicke-Korsakoff syndrome. Finally the thiamine dependent compounds acetylphosphate and acetoin, have not been studied in thiamine deficient brain. We propose a series of experiments in which thiamine deficiency will be produced in rats by dietary means. When symptomatic, we will a) evaluate metabolic flux in the appropriate cerebral regions, b) determine the effect of glucose, and fats and alcohol on pyruvate decarboxylase and metabolic flux, and c) briefly examine the effect of thiamine deficiency on acetyl phosphate and acetoin. These experiments are designed to further elucidate the underlying biochemical derrangement of thiamine deficiency which is responsible for the symptoms of both Wernicke's encephalopathy, and Korsakoff's psychosis.